This research is designed to test the hypothesis that the observed pharmacological interactions between delta a-tetrahydrocannabinol (THC) and ethanol, barbiturates, cannabidial, SKF-525A or phencyclidine result in part from metabolic interactions. Pharmacokinetics will be applied to the isolated perfused rat liver system to compare the clearance of THC and extent of active metabolite production in normal and drug pre-treated livers. THC and cannabidial will be evaluated pharmacokinetically as enzyme inducers. THC and cannabidial will be evaluated pharmacokinetically as enzyme inducers. THC metabolites will be separated, quantified and analyzed by high-pressure liquid chromatography. The hypothesis that THC can alter the rate and extent of metabolism of other drugs will be tested using pentobarbital as the model compound. These studies will serve to evaluate the isolated perfused rat liver system as a tool for studying other drug-drug interactions.